Structure and Intrinsic Disorder in Enzymology

1st Edition - November 17, 2022
Editors: Munishwar Nath Gupta, Vladimir N. Uversky
Language: English
Paperback ISBN:
9 7 8 - 0 - 3 2 3 - 9 9 5 3 3 - 7
eBook ISBN:
9 7 8 - 0 - 3 2 3 - 9 9 5 3 4 - 4

Structure and Intrinsic Disorder in Enzymology offers a direct, yet comprehensive presentation of the fundamental concepts, characteristics and functions of intrinsically disordere… Read more

Purchase options

SUSTAINABLE DEVELOPMENT

Innovate. Sustain. Transform.

Save up to 30% on top Physical Sciences & Engineering titles!

Explore now

Physical science & engineering for sustainable development book covers

Institutional subscription on ScienceDirect

Request a sales quote

Structure and Intrinsic Disorder in Enzymology offers a direct, yet comprehensive presentation of the fundamental concepts, characteristics and functions of intrinsically disordered enzymes, along with valuable notes and technical insights powering new research in this emerging field. Here, more than twenty international experts examine protein flexibility and cryo-enzymology, hierarchies of intrinsic disorder, methods for measurement of disorder in proteins, bioinformatics tools for predictions of structure, disorder and function, protein promiscuity, protein moonlighting, globular enzymes, intrinsic disorder and allosteric regulation, protein crowding, intrinsic disorder in post-translational, and much more.

Chapters also review methods for study, as well as evolving technology to support new research across academic, industrial and pharmaceutical labs.

Cover image
Title page
Table of Contents
Copyright
List of contributors
Preface
Chapter 1. Enzymology: early insights
Abstract
1.1 Introduction
1.2 Isolation and purification of proteins
1.3 The dawn of structural biology
1.4 The early work on enzyme kinetics
1.5 Assaying enzymes
1.6 Enzyme immobilization
1.7 Applied enzymology and white biotechnology
1.8 Enzymes in neat solvents
1.9 Some myths about applications of enzymes
1.10 Conclusions
References
Chapter 2. Deep mutational scanning to probe specificity determinants in proteins
Abstract
2.1 Proteins, enzymes, and disorder
2.2 Deep mutational scanning—a high-throughput method to explore protein sequence–function landscapes
2.3 Deep mutational scanning of globular proteins
2.4 Study of sequence–disorder–function relationships in Intrinsically Disordered Proteins (IDPs)
2.5 Discussion
Acknowledgments
Author contributions
References
Chapter 3. Protein flexibility and cryoenzymology: the trade-off between stability and catalytic rates
Abstract
Abbreviations
3.1 Origin of cryoenzymology
3.2 Search for the solvents suitable for the low-temperature studies
3.3 Looking into the protein folding at subzero temperatures
3.4 Cryoenzymology: analysis of the enzymatic reactions at subzero temperatures
3.5 X-ray cryoenzymology
3.6 Cryo-electron microscopy enzymology
3.7 Cryoenzymology and psychrophiles
3.8 Concluding remarks
References
Chapter 4. Thermodynamic perspective of protein disorder and phase separation: model systems
Abstract
4.1 Introduction
4.2 Conformational landscapes
4.3 Determinants of the disordered ensemble
4.4 Lessons from a protein backbone model
4.5 Aggregation of many peptides—liquid–liquid phase separation is a type of order
4.6 Future perspectives
Acknowledgments
References
Chapter 5. Structure and disorder: protein functions depend on this new binary transforming lock-and-key into structure-function continuum
Abstract
5.1 Introduction
5.2 Keys in locks and hands in gloves: classical representations of protein functionality
5.3 Structure-function paradigm cannot be stretched far enough to include protein “moonlighting,” multifunctionality, binding promiscuity, and scaffolding
5.4 A new player in the block: functional proteins without unique structures
5.5 Structural heterogeneity of IDPs and IDRs
5.6 Proteoforms as a solution for the “one gene–many proteins” challenge
5.7 Intrinsic disorder, proteoforms, and protein-structure continuum
References
Chapter 6. Methods for measuring structural disorder in proteins
Abstract
6.1 Introduction
6.2 Obtaining hints of intrinsic disorder
6.3 Assessing protein hydrodynamic properties
6.4 Assessing protein secondary structure content
6.5 Assessing protein tertiary structure
6.6 High-speed atomic force microscopy
6.7 Approaches relying on protein labeling and/or site-directed mutagenesis
6.8 In vivo assessment of disorder
6.9 Modeling intrinsically disordered proteins as conformational ensembles
6.10 Assessing binding events
Acknowledgments
References
Chapter 7. Prediction of protein structure and intrinsic disorder in the era of deep learning
Abstract
7.1 Introduction
7.2 A brief overview of protein structure prediction approaches
7.3 Critical assessment of structure prediction—structure prediction evaluation
7.4 Machine learning revolution through deep learning
7.5 Deep learning methods in structure prediction
7.6 Predicting protein disorder
7.7 Predicting the functions of disordered regions
7.8 Conclusions
References
Chapter 8. Roles of intrinsically disordered regions in phosphoinositide 3-kinase biocatalysis
Abstract
8.1 Biochemistry of PI3K enzymes
8.2 Class I PI3K enzymes
8.3 Class II PI3K enzymes
8.4 Class III PI3K enzyme
8.5 Normal and aberrant cellular functions of PI3K enzymes
8.6 Normal functions of class I PI3K in cellular signaling and physiology
8.7 Aberrant hyperactivation of PI3K as a major driver of diseases
8.8 Structural biology and biocatalysis of class I PI3K family
8.9 Role of intrinsically disordered regions in the PI3K functions
References
Chapter 9. The various facets of protein promiscuity: not just broad specificity of proteins
Abstract
9.1 Introduction
9.2 Protein specificity
9.3 Protein promiscuity as a driver of protein evolution
9.4 Types of promiscuity
9.5 Promiscuity of alkaline phosphatase superfamily
9.6 Quantifying enzyme promiscuity
9.7 Engineering enzyme promiscuity
9.8 Promiscuity in protein–protein interactions
9.9 Calmodulin promiscuity
9.10 α-Synuclein promiscuity, multifunctionality, and polypathogenicity
9.11 Promiscuity in drug design
9.12 Conclusions
References
Chapter 10. Role of plasticity and disorder in protein moonlighting: blurring of lines between biocatalysts and other biologically active proteins
Abstract
10.1 Introduction
10.2 Description of “moonlighting” as a phenomenon
10.3 What is a binding site?
10.4 Moonlighting proteins in health and diseases
10.5 Protein conformational plasticity
10.6 Disordered moonlighting regions
10.7 Intrinsic disorder roots of moonlighting: multifunctionality as a consequence of the disorder-based structural heterogeneity
10.8 Moonlighting in virulence activity of pathogens
10.9 Conclusions and future perspectives
References
Chapter 11. Molten globular enzymes
Abstract
Abbreviations
11.1 Enzymes as a cornerstone of the “lock-and-key” model of protein functionality
11.2 Molten globular enzymes: machines at the edge of stability
11.3 Concluding remarks
Acknowledgments
References
Chapter 12. Intrinsic disorder and allosteric regulation
Abstract
12.1 The ensemble view of allostery and its applications
12.2 The role of intrinsic disorder in protein allosteric regulation: representative cases
12.3 Small allosteric molecules targeting intrinsically disordered proteins
12.4 Allostery of multidomain proteins with disordered linkers
12.5 Phase separation of intrinsically disordered proteins
12.6 Computational methods to study allostery in disordered proteins and mechanism of phase separation
12.7 Outlook
References
Chapter 13. Macromolecular crowding: how it affects protein structure, disorder, and catalysis
Abstract
13.1 Introduction
13.2 What do we know about crowding inside cells?
13.3 Crowding agents employed to simulate intracellular environments
13.4 How crowding affects catalytic activity of enzymes
13.5 Effect of crowding on proteins with intrinsic disorder
13.6 Effect of crowding on protein assembly, aggregation, and amyloid formation
13.7 Miscellaneous recent observations
13.8 Conclusions and future perspectives
References
Chapter 14. Intrinsic disorder and posttranslational modification: an evolutionary perspective
Abstract
14.1 Introduction
14.2 PTMs prevail in intrinsically disordered regions and intrinsically disordered regions are enriched in PTMs
14.3 Links between posttranslational modification and disorder-to-order transitions of IDRs
14.4 An evolutionary perspective
14.5 Intrinsically disordered regions as fertile substrates for the evolution of posttranslational modification cross talk
14.6 Conclusions
References
Chapter 15. The roles of prion-like domains in amyloid formation, phase separation, and solubility
Abstract
15.1 Discovery of yeast prion proteins
15.2 Prion domains
15.3 Amyloid fibrils
15.4 Kinetics and thermodynamics of amyloid formation
15.5 Prions as protein-based genetic elements
15.6 Stable, nontransmissible assemblies as a form of cellular memory
15.7 PrLDs in the formation of biomolecular condensates
15.8 FUS as a model for LLPS by PrLDs
15.9 Misregulation of phase behavior
15.10 PrLDs as regulators of phase behavior
15.11 Conclusion
Acknowledgments
References
Chapter 16. Disordered protein networks as mechanistic drivers of membrane remodeling and endocytosis
Abstract
16.1 Introduction
16.2 Disordered proteins as sensors of membrane curvature
16.3 Disordered protein networks as catalysts of trafficking vesicle assembly
16.4 Disordered proteins as drivers of membrane curvature
16.5 Disordered protein networks as drivers of vesicle coating
16.6 Disordered proteins as drivers of vesicle uncoating
16.7 Conclusion and outlook
Acknowledgments
References
Chapter 17. How binding to surfaces affects disorder?
Abstract
17.1 Introduction
17.2 Lipid bilayers
17.3 Membrane fusion
17.4 Membrane curvature
17.5 Hemifusion stalk
17.6 The fusion pore
17.7 Membrane proteins
17.8 Binding proteins to surfaces
17.9 Synaptotagmin-1 C2A and C2B domains
17.10 The Bin/Amphiphysin/Rvs domain with an N-terminal amphipathic helix
17.11 The dynamin family
17.12 Intrinsic disorder
17.13 The acrosome reaction
17.14 Proteins within the acrosome reaction
17.15 α-Synuclein
17.16 Computational methods
17.17 Collective variables
17.18 Coordination and radial distribution function
17.19 Radius of gyration
17.20 Root mean square fluctuations
17.21 Lindemann disorder index
17.22 Conclusions
References
Index

Munishwar Nath Gupta

Dr. Munishwar Nath Gupta earned his PhD from Indian Institute of Science, Bengaluru, and completed post-doctoral positions at Massachusetts Institute of Technology (USA), University of Minnesota (USA), Lund University (Sweden), and University of Technology of Compiegne (France). He has taught chemistry, biochemistry, and biotechnology at the Indian Institute of Technology, Delhi, between 1975-2016. He was awarded the National Science Talent fellowship (India) and Fellowships of National Academy of Sciences and Indian National Science Academy. He has edited three books on thermostability of enzymes, non-aqueous enzymology and affinity-based separation methods. He was an Associate Editor of Biocatalysis and Biotransformation (Taylor and Francis) and the founding and former editor-in-chief of Sustainable Chemical Processes (Springer). He’s served on editorial boards of several national and international journals and acted as a consultant to Novozyme (Denmark), Dabur (India), and other international companies.

Affiliations and expertise

Former Emeritus Professor, Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology, Delhi, India

Vladimir N. Uversky

Prof. Vladimir N. Uversky, PhD, DSc, FRSB, FRSC, FAIMBE, Professor at the Department of Molecular Medicine, Morsani College of Medicine, University of South Florida (USF), is a pioneer in the field of protein intrinsic disorder. He has made a number of groundbreaking contributions in the field of protein folding, misfolding, and intrinsic disorder. He obtained his academic degrees from Moscow Institute of Physics and Technology (Ph.D., in 1991) and from the Institute of Experimental and Theoretical Biophysics, Russian Academy of Sciences (D.Sc., in 1998). He spent his early career working mostly on protein folding at the Institute of Protein Research and the Institute for Biological Instrumentation (Russia). In 1998, moved to the University of California Santa Cruz. In 2004, joined the Indiana University−Purdue University Indianapolis as a Senior Research Professor. Since 2010, Professor Uversky is with USF, where he works on various aspects of protein intrinsic disorder phenomenon and on analysis of protein folding and misfolding processes. Prof. Uversky has authored over 1250 scientific publications and edited several books and book series on protein structure, function, folding, misfolding, and intrinsic disorder. He is also serving as an editor in a number of scientific journals. He was a co-founder of the Intrinsically Disordered Proteins Subgroup at the Biophysical Society and the Intrinsically Disordered Proteins Gordon Research Conference. Prof. Uversky collaborated with more than 12,500 colleagues from more than 2,750 research organizations in 89 countries/territories.

Affiliations and expertise

PhD, DSc, FRSB, FRSC, FAIMBE, Professor at the Department of Molecular Medicine, Morsani College of Medicine, University of South Florida

Life Sciences

Physical Sciences & Engineering

Social Sciences & Humanities

Health